2-Azabicyclo2.2.1!hept-5-en-3-one is a useful intermediate for the manufacture of pharmaceutical entities. In particular, it can be used to prepare carbocyclic nucleosides which differ from the natural ribosyl nucleosides in having oxygen replaced by a methylene. Various carboxylic nucleosides have been demonstrated to possess useful therapeutic activity, for instance as antivirals and cardiac vasodilators. For the therapeutic purpose, it is preferred that the agents are obtained in single-enantiomer form, and this is conveniently accomplished by the use of the single enantiomers of the bicyclic lactam or derivatives thereof.
Various processes for obtaining the enantiomers of the bicyclic lactam are known. EP-A-0424064 discloses biocatalytic hydrolysis with enzymes that have a preference for one or other isomer, so that after the biotransformation of racemic lactam there are obtained one enantiomer as the untransformed lactam and the other enantiomer as ring-opened amino-acid. More recently, resolution of the bicyclic lactam through lipase-mediated resolution of the N-hydroxymethyl derivative has been reported by Nakano et al, Tetrahedron Asymmetry, 5: 1155-56 (1994).